scholarly journals Dietary Eriodictyol Alleviates Adiposity, Hepatic Steatosis, Insulin Resistance, and Inflammation in Diet-Induced Obese Mice

2019 ◽  
Vol 20 (5) ◽  
pp. 1227 ◽  
Author(s):  
Eun-Young Kwon ◽  
Myung-Sook Choi
Keyword(s):  
Insulin Resistance ◽  
Hepatic Steatosis ◽  
Molecular Mechanisms ◽  
Gastric Inhibitory Polypeptide ◽  
Normal Diet ◽  
Acid Oxidation ◽  
Obese Mice ◽  
Metabolic Disturbances ◽  
Glucagon Like Peptide 1 ◽  
Hepatic Fatty Acid Oxidation

The present study aimed to investigate the molecular mechanisms underlying the anti-obesity effect of flavonoid eriodictyol (ED) supplementation in mice fed with a high-fat diet (HFD). C57BL/6N mice were fed with normal diet (ND), HFD (40 kcal% fat), or HFD + 0.005% (w/w) ED for 16 weeks. In HFD-induced obese mice, dietary ED supplementation significantly alleviated dyslipidemia and adiposity by downregulating the expression of lipogenesis-related genes in white adipose tissue (WAT), while enhancing fecal lipid excretion. ED additionally improved hepatic steatosis and decreased the production of pro-inflammatory cytokines by downregulating the expression of hepatic enzymes and the genes involved in lipogenesis and upregulating the expression of hepatic fatty acid oxidation-related enzymes and genes. In addition, ED improved insulin resistance (IR) by suppressing hepatic gluconeogenesis, enhancing glucose utilization, and modulating the production and release of two incretin hormones, namely gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). Taken together, the current findings indicated that ED can protect against diet-induced obesity and related metabolic disturbances, including dyslipidemia, inflammation, fatty liver disease, and IR in diet-induced obese mice.

scholarly journals Glucocorticoid-Induced Metabolic Disturbances are Exacerbated in Obesity

2017 ◽  
Author(s):  
Innocence Harvey ◽  
Erin J. Stephenson ◽  
JeAnna R. Redd ◽  
Quynh T. Tran ◽  
Irit Hochberg ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Liver ◽  
Hepatic Steatosis ◽  
Adult Male ◽  
Synergistic Effects ◽  
Lipolytic Enzyme ◽  
Metabolic Dysfunction ◽  
Obese Mice ◽  
Metabolic Disturbances ◽  
Diet Induced Obesity

AbstractObjective: To determine the effects of glucocorticoid-induced metabolic dysfunction in the presence of diet-induced obesity. Methods: C57BL/6J adult male lean and diet-induced obese mice were given dexamethasone for different durations and levels of hepatic steatosis, insulin resistance and lipolysis were determined. Results: Obese mice given dexamethasone had significant, synergistic effects on insulin resistance and markers of lipolysis, as well as hepatic steatosis. This was associated with synergistic transactivation of the lipolytic enzyme ATGL. Conclusions: The combination of chronically elevated glucocorticoids and obesity leads to exacerbations in metabolic dysfunction. Our findings suggest lipolysis may be a key player in glucocorticoid-induced insulin resistance and fatty liver in individuals with obesity.

scholarly journals Effects of exercise and low-fat diet on adipose tissue inflammation and metabolic complications in obese mice

2009 ◽  
Vol 296 (5) ◽  
pp. E1164-E1171 ◽  
Author(s):  
Victoria J. Vieira ◽  
Rudy J. Valentine ◽  
Kenneth R. Wilund ◽  
Nirav Antao ◽  
Tracy Baynard ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Hepatic Steatosis ◽  
Adipose Tissue Inflammation ◽  
Obese Mice ◽  
Metabolic Disturbances ◽  
Low Fat ◽  
Tissue Inflammation ◽  
Low Fat Diet ◽  
Tnf Α

Adipose tissue inflammation causes metabolic disturbances, including insulin resistance and hepatic steatosis. Exercise training (EX) may decrease adipose tissue inflammation, thereby ameliorating such disturbances, even in the absence of fat loss. The purpose of this study was to 1) compare the effects of low-fat diet (LFD), EX, and their combination on inflammation, insulin resistance, and hepatic steatosis in high-fat diet-induced obese mice and 2) determine the effect of intervention duration (i.e., 6 vs. 12 wk). C57BL/6 mice ( n = 109) fed a 45% fat diet (HFD) for 6 wk were randomly assigned to an EX (treadmill: 5 days/wk, 6 or 12 wk, 40 min/day, 65–70% V̇o2max) or sedentary (SED) group. Mice remained on HFD or were placed on a 10% fat diet (LFD) for 6 or 12 wk. Following interventions, fat pads were weighed and expressed relative to body weight; hepatic steatosis was assessed by total liver triglyceride and insulin resistance by HOMA-IR and glucose AUC. RT-PCR was used to determine adipose gene expression of MCP-1, F4/80, TNF-α, and leptin. By 12 wk, MCP-1, F4/80, and TNF-α mRNA were reduced by EX and LFD. Exercise ( P = 0.02), adiposity ( P = 0.03), and adipose F4/80 ( P = 0.02) predicted reductions in HOMA-IR ( r2 = 0.75, P < 0.001); only adiposity ( P = 0.04) predicted improvements in hepatic steatosis ( r2 = 0.51, P < 0.001). Compared with LFD, EX attenuated increases in adiposity, hepatic steatosis, and adipose MCP-1 expression from 6 to 12 wk. There are unique metabolic consequences of a sedentary lifestyle and HFD that are most evident long term, highlighting the importance of both EX and LFD in preventing obesity-related metabolic disturbances.

scholarly journals Arid1a protects against hepatic steatosis and insulin resistance via PPARα-mediated fatty acid oxidation

2019 ◽  
Author(s):  
Yu-Lan Qu ◽  
Chuan-Huai Deng ◽  
Qing Luo ◽  
Xue-Ying Shang ◽  
Jiao-Xiang Wu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Hepatic Steatosis ◽  
Fatty Acid Oxidation ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Lifestyle Changes ◽  
Health Concern ◽  
Acid Oxidation ◽  
Alcoholic Fatty Liver

AbstractNon-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) have become a worldwide health concern because of lifestyle changes, but it is still lack of specific therapeutic strategies as the underlying molecular mechanisms remain poorly understood. Our previous study indicated that deficiency of Arid1a, a key component of SWI/SNF chromatin remodeling complex, initiated mouse steatohepatitis, implying that Arid1a might be essentially required for the integrity of hepatic lipid metabolism. However, the exact mechanisms of the pathological process due to Arid1a loss are unclear. In the present work, we show that hepatocyte-specific deletion of Arid1a significantly increases susceptibility to develop hepatic steatosis and insulin resistance in mice fed with high-fat diet (HFD), along with the aggravated inflammatory responses marked by increment of serum alanine amino transferase (AST), aspartate amino transferase (AST) and TNFα. Mechanistically, Arid1a deficiency leads to the reduction of chromatin modification characteristic of transcriptional activation on multiple metabolic genes, especially Cpt1a and Acox1, two rate-limiting enzyme genes for fatty acid oxidation. Furthermore, our data indicated that Arid1a loss promotes hepatic steatosis by downregulating PPARα, thereby impairing fatty acid oxidation which leads to lipid accumulation and insulin resistance. These findings reveal that targeting ARID1a might be a promising therapeutic strategy for NAFLD, NASH and insulin resistance.

scholarly journals Carvacrol Protects against Hepatic Steatosis in Mice Fed a High-Fat Diet by Enhancing SIRT1-AMPK Signaling

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Eunkyung Kim ◽  
Youngshim Choi ◽  
Jihee Jang ◽  
Taesun Park
Keyword(s):  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Molecular Mechanisms ◽  
Plasma Concentrations ◽  
Normal Diet ◽  
Acid Oxidation ◽  
High Fat ◽  
Monocyte Chemoattractant Protein 1 ◽  
Ampk Signaling ◽  
Liver Kinase B1

We investigated the protective effect of carvacrol against high-fat-diet-induced hepatic steatosis in mice and the potential underlying molecular mechanisms. Mice were fed a normal diet, high-fat diet, or carvacrol-supplemented high-fat diet for 10 weeks. Compared to mice fed the high-fat diet, those fed the carvacrol-supplemented diet showed significantly lower hepatic lipid levels and reduced plasma activities of alanine aminotransferase and aspartate aminotransferase and plasma concentrations of monocyte chemoattractant protein 1 and tumor necrosis factorα. Carvacrol decreased the expression of LXRα, SREBP1c, FAS, leptin, and CD36 genes and phosphorylation of S6 kinase 1 protein involved in lipogenesis, whereas it increased the expression of SIRT1 and CPT1 genes and phosphorylation of liver kinase B1, AMP-activated protein kinase, and acetyl-CoA carboxylase proteins involved in fatty acid oxidation in the liver of mice fed the high-fat diet. These results suggest that carvacrol prevents HFD-induced hepatic steatosis by activating SIRT1-AMPK signaling.

scholarly journals PPARα-Deficient ob/ob Obese Mice Become More Obese and Manifest Severe Hepatic Steatosis Due to Decreased Fatty Acid Oxidation

2015 ◽  
Vol 185 (5) ◽  
pp. 1396-1408 ◽  
Author(s):  
Qian Gao ◽  
Yuzhi Jia ◽  
Gongshe Yang ◽  
Xiaohong Zhang ◽  
Prajwal C. Boddu ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Hepatic Steatosis ◽  
Fatty Acid Oxidation ◽  
Acid Oxidation ◽  
Obese Mice

Black rice anthocyanins alleviate hyperlipidemia, liver steatosis and insulin resistance by regulating lipid metabolism and gut microbiota in obese mice

2021 ◽  
Author(s):  
Haizhao Song ◽  
Xinchun Shen ◽  
Yang Zhou ◽  
Xiaodong Zheng
Keyword(s):  
Insulin Resistance ◽  
Lipid Metabolism ◽  
Gut Microbiota ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Liver Steatosis ◽  
Obese Mice ◽  
Black Rice ◽  
High Fat ◽  
Diet Induced Obesity

Supplementation of black rice anthocyanins (BRAN) alleviated high fat diet-induced obesity, insulin resistance and hepatic steatosis by improvement of lipid metabolism and modification of the gut microbiota.

scholarly journals Treatment with Lobeglitazone Attenuates Hepatic Steatosis in Diet-Induced Obese Mice

PPAR Research ◽  
2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Sorim Choung ◽  
Kyong Hye Joung ◽  
Bo Ram You ◽  
Sang Ki Park ◽  
Hyun Jin Kim ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Hepatic Steatosis ◽  
Plasma Cholesterol ◽  
Cholesterol Biosynthesis ◽  
Peroxisome Proliferator ◽  
Obese Mice ◽  
Nonalcoholic Fatty Liver ◽  
Hepatic Lipid ◽  
Hepatic Expression ◽  
Expression Of Genes

Nonalcoholic fatty liver disease (NAFLD) is strongly associated with insulin resistance. The peroxisome proliferator-activated receptor (PPAR) activators, thiazolidinediones, (TZDs), are insulin sensitizers used as a treatment for NAFLD. However, TZDs are a controversial treatment for NAFLD because of conflicting results regarding hepatic steatosis and fibrosis. To evaluate a possible effective drug for treatment of NAFLD, we investigated the effects of a newly developed TZD, lobeglitazone, with an emphasis on hepatic lipid metabolism. Lobeglitazone treatment for 4 weeks in high fat diet- (HFD-) induced obese mice (HL group) improved insulin resistance and glucose intolerance compared to HFD-induced obese mice (HU group). The gene levels related to hepatic gluconeogenesis also decreased after treatment by lobeglitazone. The livers of mice in the HL group showed histologically reduced lipid accumulation, with lowered total plasma cholesterol and triglyceride levels. In addition, the HL group significantly decreased the hepatic expression of genes associated with lipid synthesis, cholesterol biosynthesis, and lipid droplet development and increased the hepatic expression of genes associated with fatty acid β-oxidation, thus suggesting that lobeglitazone decreased hepatic steatosis and reversed hepatic lipid dysregulation. Livers with steatohepatitis contained increased levels of PPARγ and phosphorylated PPARγ at serine 273, leading to downregulation of expression of genes associated with insulin sensitivity. Notably, the treatment of lobeglitazone increased the protein levels of PPARα and diminished levels of PPARγ phosphorylated at serine 273, which were increased by a HFD, suggesting that induction of PPARα and posttranslational modification of PPARγ in livers by lobeglitazone might be an underlying mechanism of the improvement seen in NAFLD. Taken together, our data showed that lobeglitazone might be an effective treatment for NAFLD.

scholarly journals Metreleptin for the treatment of progressive encephalopathy with/without lipodystrophy (PELD) in a child with progressive myoclonic epilepsy: a case report

2020 ◽  
Vol 46 (1) ◽  
Author(s):  
Stefania Pedicelli ◽  
Luca de Palma ◽  
Caterina Pelosini ◽  
Marco Cappa
Keyword(s):  
Insulin Resistance ◽  
Hepatic Steatosis ◽  
Early Death ◽  
Abdominal Ultrasound ◽  
Myoclonic Epilepsy ◽  
Genetic Syndromes ◽  
Metabolic Disturbances ◽  
Psychomotor Delay ◽  
Progressive Encephalopathy ◽  
Progressive Myoclonic Epilepsy

Abstract Background A number of genetic syndromes associated with variants in the BSCL2/seipin gene have been identified. Variants that cause skipping of exon 7 are associated with progressive encephalopathy with/without lipodystrophy (PELD), which is characterized by the development of progressive myoclonic epilepsy at a young age, severe progressive neurological impairment, and early death, often in childhood. Because the genetic basis of PELD is similar to that of congenital lipodystrophy type 2, we hypothesized that a patient with PELD may respond to treatments approved for other congenital lipodystrophic syndromes. Case presentation We describe a 5-year-old boy with an extremely rare phenotype involving severe progressive myoclonic epilepsy who received metreleptin (a recombinant analogue of leptin) to control metabolic abnormalities. At the age of two, he had no subcutaneous adipose tissue, with hypertriglyceridemia, hypertransaminasemia and hepatic steatosis. He also had a moderate psychomotor delay and generalized tonic seizures. At 4 years, he had insulin resistance, hypercholesterolemia, hypertriglyceridemia, mild hepatosplenomegaly and mild hepatic steatosis; he began a hypolipidemic diet. Severe psychomotor delay and myoclonic/myoclonic atonic seizures with absences was evident. At 5 years of age, metreleptin 0.06 mg/kg/day was initiated; after 2 months, the patient’s lipid profile improved and insulin resistance resolved. After 1 year of treatment, hepatic steatosis improved and abdominal ultrasound showed only mild hepatomegaly. Seizure frequency decreased but was not eliminated during metreleptin therapy. Conclusions Metreleptin may be used to control metabolic disturbances and may lead to better seizure control in children with PELD.

Biochanin A improves hepatic steatosis and insulin resistance by regulating the hepatic lipid and glucose metabolic pathways in diet-induced obese mice

2016 ◽  
Vol 60 (9) ◽  
pp. 1944-1955 ◽  
Author(s):  
Hee-Sook Park ◽  
Haeng Jeon Hur ◽  
Soon-Hee Kim ◽  
Su-Jin Park ◽  
Moon Ju Hong ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Hepatic Steatosis ◽  
Metabolic Pathways ◽  
Biochanin A ◽  
Obese Mice ◽  
Hepatic Lipid

scholarly journals Peripancreatic adipose tissue protects against high-fat-diet-induced hepatic steatosis and insulin resistance in mice

2020 ◽  
Vol 44 (11) ◽  
pp. 2323-2334
Author(s):  
Belén Chanclón ◽  
Yanling Wu ◽  
Milica Vujičić ◽  
Marco Bauzá-Thorbrügge ◽  
Elin Banke ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Adipose Tissue ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Obese Mice ◽  
High Fat ◽  
Insulin Levels ◽  
Fat Depots ◽  
Fat Depot

Abstract Background/objectives Visceral adiposity is associated with increased diabetes risk, while expansion of subcutaneous adipose tissue may be protective. However, the visceral compartment contains different fat depots. Peripancreatic adipose tissue (PAT) is an understudied visceral fat depot. Here, we aimed to define PAT functionality in lean and high-fat-diet (HFD)-induced obese mice. Subjects/methods Four adipose tissue depots (inguinal, mesenteric, gonadal, and peripancreatic adipose tissue) from chow- and HFD-fed male mice were compared with respect to adipocyte size (n = 4–5/group), cellular composition (FACS analysis, n = 5–6/group), lipogenesis and lipolysis (n = 3/group), and gene expression (n = 6–10/group). Radioactive tracers were used to compare lipid and glucose metabolism between these four fat depots in vivo (n = 5–11/group). To determine the role of PAT in obesity-associated metabolic disturbances, PAT was surgically removed prior to challenging the mice with HFD. PAT-ectomized mice were compared to sham controls with respect to glucose tolerance, basal and glucose-stimulated insulin levels, hepatic and pancreatic steatosis, and gene expression (n = 8–10/group). Results We found that PAT is a tiny fat depot (~0.2% of the total fat mass) containing relatively small adipocytes and many “non-adipocytes” such as leukocytes and fibroblasts. PAT was distinguished from the other fat depots by increased glucose uptake and increased fatty acid oxidation in both lean and obese mice. Moreover, PAT was the only fat depot where the tissue weight correlated positively with liver weight in obese mice (R = 0.65; p = 0.009). Surgical removal of PAT followed by 16-week HFD feeding was associated with aggravated hepatic steatosis (p = 0.008) and higher basal (p < 0.05) and glucose-stimulated insulin levels (p < 0.01). PAT removal also led to enlarged pancreatic islets and increased pancreatic expression of markers of glucose-stimulated insulin secretion and islet development (p < 0.05). Conclusions PAT is a small metabolically highly active fat depot that plays a previously unrecognized role in the pathogenesis of hepatic steatosis and insulin resistance in advanced obesity.

Sign in / Sign up

Export Citation Format

Share Document